Borderline personality disorder (BOR) is determined by environmental and genetic factors,
and characterized by affective instability and impulsivity, diagnostic symptoms also observed
in manic phases of Bipolar Disorder (BIP). Up to 20% of BIP patients show comorbidity with
BOR. This report describes the first case-control genome-wide association study (GWAS) of
BOR, performed in one of the largest BOR patient samples worldwide. The focus of our
analysis was: (i) to detect genes and gene-sets involved in BOR; and (ii) to investigate the
genetic overlap with BIP. As there is considerable genetic overlap between BIP, Major
Depression (MDD) and Schizophrenia (SCZ) and a high comorbidity of BOR and MDD, we
also analyzed the genetic overlap of BOR with SCZ and MDD. GWAS, gene-based tests,and gene-set-analyses were performed in 998 BOR patients and 1,545 controls. LD score
regression was used to detect genetic overlap between BOR and these disorders. Single
marker analysis revealed no significant association after correction for multiple testing. Genebased
analysis yielded two significant genes: DPYD (p=4.42x10-7) and PKP4 (p=8.67x10-7);
and gene-set-analysis yielded a significant finding for exocytosis (GO:0006887, pFDR=0.019).
Prior studies have implicated DPYD, PKP4 and exocytosis in BIP and SCZ. The most
notable finding of the present study was the genetic overlap of BOR with BIP (rg=0.28
[p=2.99x10-3]), SCZ (rg=0.34 [p=4.37x10-5]), and MDD (rg=0.57 [p=1.04x10-3]). Our study is
the first to demonstrate that BOR overlaps with BIP, MDD and SCZ on the genetic level.
Whether this is confined to transdiagnostic clinical symptoms should be examined in future
studies
